What are the dosing recommendations for lefunomide in patients with impaired renal function?

Leflunomide Dosing in Renal Impairment

Leflunomide does not require dose adjustment in patients with renal impairment, including those with severe renal dysfunction or on hemodialysis. 1, 2

Pharmacokinetics and Renal Handling

• Leflunomide is metabolized to its active form A771726, which does not rely primarily on renal excretion for elimination 2
• Studies have demonstrated that steady-state concentrations of the active metabolite A771726 are not significantly affected by hemodialysis or renal impairment 2
• Unlike many other antirheumatic medications, leflunomide can be used without dosage modification in patients with reduced renal function 1

Dosing Recommendations

• Standard dosing of leflunomide can be maintained regardless of renal function status 1
• The typical dosing regimen (loading dose of 100 mg followed by maintenance dose of 10-20 mg daily) remains appropriate for patients with renal impairment 2
• Hemodialysis does not significantly alter plasma concentrations of leflunomide's active metabolite, making supplemental dosing after dialysis unnecessary 2

Monitoring Considerations

• While dose adjustment is not required, patients with renal impairment should still undergo regular monitoring of:
  • Liver function tests (particularly important as elevated liver enzymes may occur) 2
  • Complete blood counts to monitor for potential hematologic effects 1
  • Clinical efficacy and potential adverse effects 2

Contrast with Other Antirheumatic Medications

• Unlike leflunomide, many other antirheumatic drugs require significant dosage adjustments in renal impairment:
  • Methotrexate should be avoided in patients with eGFR < 45 ml/min due to risk of fatal pancytopenia 1
  • Sulfasalazine, azathioprine, mycophenolate mofetil, cyclophosphamide, and antimalarials require dose reductions in moderate to severe renal impairment 1
  • NSAIDs, COX-2 inhibitors, gold, and cyclosporine have limited use in renal impairment due to nephrotoxicity 1

Clinical Considerations

• Despite the lack of need for dose adjustment, caution is still warranted when using leflunomide in patients with renal impairment due to:
  • Increased risk of infections in immunosuppressed patients with renal dysfunction 1
  • Potential for drug interactions with other medications commonly used in patients with renal impairment 3
  • Inconsistency in dosing information across drug information sources, highlighting the importance of consulting current evidence 3, 4

Practical Application

• For patients transitioning from other antirheumatic drugs to leflunomide due to renal concerns, standard loading and maintenance doses can be used 2
• In patients with end-stage renal disease on hemodialysis, leflunomide can be administered without timing considerations related to dialysis sessions 2
• Monitor liver function tests regularly, as dose reductions may be needed if hepatic enzyme elevations occur, independent of renal function 2